Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents

Toyoaki Hida; Ken-Ichi Kozaki; Hidemi Ito; Osamu Miyaishi; Yoshio Tatematsu; Takeshi Suzuki; Keitaro Matsuo; Takahiko Sugiura; Makoto Ogawa; Toshitada Takahashi; Takashi Takahashi

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents

Clin Cancer Res. 2002 Jul;8(7):2443-7.

Authors

Toyoaki Hida¹, Ken-Ichi Kozaki, Hidemi Ito, Osamu Miyaishi, Yoshio Tatematsu, Takeshi Suzuki, Keitaro Matsuo, Takahiko Sugiura, Makoto Ogawa, Toshitada Takahashi, Takashi Takahashi

Affiliation

¹ Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan. [email protected]

PMID: 12114451

Abstract

This study reports that a selective COX-2 inhibitor JTE-522inhibits both in vitro and in vivo growth of human lung cancer cells as a single agent. Furthermore, the adjunct use of JTE-522 is shown to significantly enhance treatment efficacy of conventional anticancer drugs not only in vitro but also in vivo without causing any noticeable side effects. Indeed, IC(50)s of various anticancer agents in vitro were reduced by up to 70%, whereas the combination therapy of JTE-522 with docetaxel and vinorelbine inhibited tumor growth in vivo by 65 and 55%, respectively. Taken together, these findings suggest that the use of a selective COX-2 inhibitor in the treatment of lung cancer may be promising, especially because of its enhancement of the treatment efficacy of conventional anticancer agents without compromising quality of life.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy*
Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Animals
Anthracyclines*
Antibiotics, Antineoplastic / pharmacology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Benzenesulfonates / therapeutic use*
Cell Division / drug effects
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / therapeutic use*
Docetaxel
Drug Resistance, Neoplasm
Female
Humans
In Vitro Techniques
Isoenzymes / antagonists & inhibitors*
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Membrane Proteins
Mice
Mice, Nude
Neoplasm Transplantation
Oxazoles / therapeutic use*
Paclitaxel / administration & dosage
Paclitaxel / analogs & derivatives*
Prostaglandin-Endoperoxide Synthases
Taxoids*
Tumor Cells, Cultured / drug effects
Vinblastine / administration & dosage
Vinblastine / analogs & derivatives*
Vinorelbine

Substances

4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
Anthracyclines
Antibiotics, Antineoplastic
Benzenesulfonates
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Membrane Proteins
Oxazoles
Taxoids
Docetaxel
Vinblastine
amrubicin
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases
Paclitaxel
Vinorelbine